The proposed research project is an attempt to elucidate the primary defect in the development of a genetic cardiomyopathy. The cardiomyopathic Syrian hamster has been chosen as our model as it provides a system in which one can study cellular alterations similar to those observed in non-vascular cardiomyopathies seen in man. It will be an inter-disciplinary approach, utilizing quantitative electron microscopy, biochemistry, electrophysiology, and tissue culture techniques. Specifically, quantitative electron microscopy will reveal morphological alterations in the normal development of the mammalian heart and this will be compared to development of the myopathic myocardium. Quantitative and kinetic aspects of cellular, mitochondrial and sarcoplasmic reticular calcium handling will be investigated, since alterations in myocardial calcium metabolism have been implicated in the disease process. Myocardial contractility will be measured in normal and diseased hamsters. Tissue culture will allow an analysis of exogenous factors (hormones, etc.) which might affect the development and course of the myopath, as well as provide a method of analysis of drugs, etc. that might prevent or delay myopathic development. It is hoped that such an integrated approach will aid in our understanding of myocardial failure as well as normal developmental processes. BIBLIOGRAPHIC REFERENCES: Colgan, J., Sachs, H., and Lazarus, M. Quantitative Electron Microscopy of Cardiomyopathy. Anatomical Record 181 #2:335, 1975. Lazarus, M., Colgan, J., and Sachs, H. Quantitative Ultrastructural Measurements on a Genetic Cardiomyopathy. Circulation 52 #4, Suppl. II-41, 1975.